.com
.gov
.org
First telerobotic
surgical system
First assigned domain
names
New drug for
lymphoma
R
Computer mouse
U.S. Dept. of
Education 2010
technology plan
Ultrasound for
medical diagnostics
Treatment for
d rug-resistant malaria
First ARPANET and
internetworking nodes
Emmy Awards for
HDTV
and more
Created Siri
(acquired by Apple)
A Research and Innovation Center
© 2016 SRI International
1
SRI’s Mission:
create world changing solutions
making people safer, healthier, and
more productive
Not-for-profit :
Return on investment is
measured by impact,
Science-focused:
Build on technology platforms
Multidisciplinary:
Perspective:
Breadth and depth to solve the
Located in the heart of silicon
hardest problems
valley, 100s of partners around
to fill gaps in customer needs
not dollars
the globe
© 2016 SRI International
2
SRI – Who We Are
A world-leading independent R&D organization
•
•
•
Founded by Stanford in 1946
− Located in heart of Silicon Valley
− More than 10 locations worldwide
− Not-for-profit corporation
− Independent in 1970
2,100 staff members
− More than half with advanced degrees
Consolidated 2015 revenue ~$550M
Headquarters — Menlo Park, California
Princeton, New Jersey
3
© 2016 SRI International
Bridging Basic Research to Commercialization
Easy to describe, very challenging to do!
“Valley of Death”
Corporations
Universities
and National
Laboratories
Discovery
Basic
Research
Applied
Research
© 2012 SRI International
© 2016 SRI International
Product
Development
Production
Bridging Basic Research to Commercialization
Easy to describe, very challenging to do !
SRI
Universities
and National
Laboratories
Discovery
Basic
Research
Applied
Research
© 2016 SRI International
Corporations
Product
Development
Production
Our legacy of world-changing innovations
.com
.gov
.org
First computer mouse
Created Siri
(acquired by Apple)
First ARPANET and
internetworking nodes
First telerobotic
surgical system
Ultrasound for
medical diagnostics
New drug for lymphoma
U.S. Dept. of Education 2010
technology plan
Emmy Awards for HDTV
and more
Developed SWOT analysis
1 st Disneyland theme park
Vision technologies
(HDTV, Color TV, etc.)
© 2016 SRI International
First assigned domain names
Converting government investment to market impact
Products
Scale Up & Licenses
Non-Profit Retain IP
Ventures
SRI Global
Partnerships
© 2016 SRI International
SRI Technology Spin-off Ventures
Publicly Traded
Robotics
DNA testing services*
Surgical robotics
Speech recognition
for customer service
Electroadhesion for
materials handling
Innovative robots for
manufacturing/service*
Soft robotics for
Medical rehabilitation
Information Technology
Virtual personal
travel guide
Artificial intelligence for
web personalization
Real-time web video
streaming and
sharing
Intelligent banking
Artificial intelligence for
calendar integration
Iris biometric
identification*
Virtual personal
assistant for smart phones*
Customer service
tools*
Materials
Electroactive polymers*
Enterprise social
media technology*
Digital TV technologies*
Stray voltage detection
services
Panoramic image
editing software*
Electronic and digital
signature solutions
Technology for K-12 and
higher education
Bio/Medical
Anti-counterfeiting
systems*
Environmentally friendly
light products*
Digital color printing
applications*
Metal “print and plate”
manufacturing process
(formerly Rosedale Medical)
Super-bright LED
light engines*
Optical network
components
Drug dispensing system*
Disposable hearing aid*
Drug discovery
Glucose monitoring system
Bed bug detection devices
*Acquired or merged
© 2016 SRI International
100+ industry projects annually
•
S/W stabilization for mobile chat - - Google
•
Mobile Banking assistant
- BBVA (Spain)
•
Medical device for continuous
blood pressure measurement
- Omron
•
Long-range Iris Biometrics
- Client private
•
Vehicle-to-vehicle communications - GM
•
Dioxin abatement
- Mitsui Heavy Industries (Japan)
•
Content summarization
- Yahoo
•
Underwater Mass Spectromete
- Chevron
•
Educational Products
- Microsoft
•
And many more …
•
•
•
•
•
Activity monitoring algorithms
- Client private
Automotive lane sensing
- Volvo
Scientific digital imagers
- Perkin-Elmer
Pharmaceutical development
- Roche
Electro-adhesion Floor Cleaner
- Client Private (Japan)
© 2016 SRI International
Key Success Factor = How We Work
5 Disciplines of Innovation enable success
1
Important customer or market needs
2
High value creation
3
Innovation champions
4
Innovation teams
5
Organizational alignment
Top 10 book
10
© 2016 SRI International
SRI technology platforms in computing, robotics,
sensors, materials, biomedical science and health.
A.I. & Computer Speech & Vision
Science
Technology
Robotics &
Automation
• Machine
learning
• Virtual Assistants
• Structured
analysis
• Knowledge
representation
• Workflow
automation
• Activity
recognition
• Cyber & security
• Speech
recognition
• Translation
• Language
analytics
• Emotion and
state
• Speaker ID
• Natural language
• Manipulation
• Mobility
• Micro-robots
• Trusted systems
• Image
processing
• Perception
• Visual search
• Augmented/Virt
ual reality
• Object and
activity
recognition
• Biometrics
• Data analytics
• Automated
reasoning
• Cyberphysical
systems
SRI
• Computational
imaging
Technology Platforms
• Actuators
• Automation
systems
• Machine
learning
• Perception
• SLAM
• Electro-active
materials
Sensing &
Devices
• Multi-spectral
imagers
• Medical devices
• RF, Radars
• Chemical
• Optics and
Lasers
• Molecular/DNA
• Input and
gesture
• Physiological
monitoring
Energy &
Materials
Biomedical
Science & Health
• Custom polymers • Drug Discovery
• Low cost silicon
• Preclinical Development
• Carbon capture
• Early Clinical Trials
• Biofuels
• Neuroscience
• Gas separations
• Infectious Disease
• Water
purification
• Oncology
• Bioinformatics
• Biomarkers
• Efficient energy
• Proteomics
transfer
• Sustainable
• Glycomics
materials
• Diagnostics
• Circulating Tumor Cells
• Biomedical Imaging
• Medicinal Chemistry
• HTS/HCS
• Aging Research Initiative
Combine and Customize
© 2016 SRI International
Unique Client Solution
Lab to Market Ideation Process
Strategic
Landscape
Identify major
market trends &
the business
context of our
customers
Customer Need
Statement
Learn customer
business and
technical challenges
and use cases
Ideation
Workshop
Create technical
solution concept,
scope and timeline
© 2016 SRI International
Selection
Prioritize and
determine phased
implementation
strategy
SRI’s innovation acceleration model
Execute
Engage
Discover
Ideation Workshop
Identify internal and
external technology /
market baseline. Generate
use case scenarios &
product / service offerings
linked to innovative use of
SRI technology platforms.
Build short and longer term
roadmaps
Ideation
1 - 3 months
Phased Development Program
Rapid & Iterative Lab-to-Market Model
Transition
Proof of
Concept
Prototype
Client Review
SRI Technology Platforms
to Client
Client Review
Custom Solution
9 - 18 months
Innovation Programs
Applying SRI’s value creation process to identify, evaluate and transform organizational innovation practices.
Impact
© 2016 SRI International
13
Case Study: SRI Lab to Market
2003 to 2008 – DARPA initiates new R&D program called
Cognitive Assistant that Learns and Organizes (CALO).
SRI selected to lead team of 20+ research organizations.
$150M funding over 5 years.
2007 – Several industrial projects with computing and mobile
electronics companies.
SRI hires Dag Kittlaus, former Motorola executive, as an EIR
(entrepreneur-in-residence) to explore market opportunities for
CALO technologies.
Late 2009 – Siri launches in app store
2008 – SRI scientist Adam Cheyer joins Dag Kittlaus and Tom
Gruber to found Siri as an SRI spin-off venture. Siri raises $8.5M
series A financing, followed by $15M series B.
May 2010 – Siri acquired by Apple
Oct 2011 – Siri integrated in iPhone 4s
© 2016 SRI International
14
Case Study: SRI Lab to
Prototype
Strategic
Landscape
Customer Need
Statement
•
Motorcycle
Fatalities
•
•
Automobile
Fatalities
We want to build safer
motorcycles
We want to increase our market
share
We want to be known as
technology leaders
© 2016 SRI International
Ideation
Workshop
Concept
Design
First trials -> less than 7 months after workshop
https://www.youtube.com/watch?v=UC56nleFKX0
© 2016 SRI International
16
Case Study: SRI Lab to License
Enhancing security and privacy for mobile
devices
Samsung sought a robust biometric experience
that was fast and simple to use. Utilizing SRI’s
Iris On-the Move (IOM™) technology, Samsung
and SRI were able to develop a compact, lowcost H/W and S/W module that was safe, secure,
and easy-to-use.
Result:
• 1000x smaller
• 100x lower-cost
• 10x faster
Samsung entered into a license for technology
and continues to work with SRI to develop both
industrial and consumer applications of mobile
IOM™.
17
Biosciences
Basic biomedical research
Drug and diagnostics
discovery
© 2016 SRI International
Preclinical and clinical
development
Our Impact on World Health
More than six decades of breakthroughs
Halofantrine
SRI-discovered halofantrine,
marketed as Halfan® by
GlaxoSmithKline and
distributed by the World
Health Organization, has saved
countless lives as a treatment
for drug-resistant malaria.
Pralatrexate
For treatment of T-cell
lymphoma, the FDA
approved pralatrexate,
co-discovered by SRI and
marketed as Folotyn®
by Allos
Bexarotene
SRI discovered Bexarotene,
a retinoid receptor ligand
marketed as Targretin® by
Eisai for treatment of
cutaneous T-cell lymphoma
© 2016 SRI International
Ultrasound
SRI made ultrasound
practical for medical
diagnostics.
Telerobotic Surgery
SRI technology allows
surgeons to remotely
perform minimally invasive
surgical procedures.
Bioinformatics
SRI ’ s genomic databases
combine with artificial
intelligence and symbolic
computing techniques to
accelerate research.
Real drugs
Halfan®
halofantrine
Antimalarial
GSK
Targretin®
bexarotene
Anticancer
Eisai
Folotyn®
pralatrexate
Anticancer
Allos
© 2016 SRI International
20
SRI Biosciences
Pharmaceutical Focus
•
300 person R&D division
− $50M annual base of gov’t-funded R&D
− $20M annual non-gov’t support
•
In typical years we team with approx.:
− 10 foundations & other nonprofits
− 20 gov’t agencies
− 30 universities
− 70 companies
© 2016 SRI International
21
SRI Biosciences
Our team
© 2016 SRI International
22
100s of Novel Drugs
$100s of Millions in R&D
Millions of Lives Saved
With Help from Many Friends
© 2016 SRI International
23
Basic Research in Disease Mechanisms
Infectious Disease
Cancer
• Tropical & neglected
diseases
• Influenza, TB
• Drug resistance
• Vector biology
• Biodefense
•
•
•
•
•
•
Akt, survivin, estrogen pathway inhibitors
Low oxygen, ischemia
Angiogenesis
Rare cell technology
Radiobiology research
Tumor glycomics
CNS Disease
Autoimmunity & Inflammation
• Aging
• Cognition
• Inflammatory & autoimmune diseases
• Innate responses
• Sleep, circadian rhythms • Adaptive responses:
• Neurodegeneration
Antigen-specific responses,
• Pain
T cell and B cell functions
• Addiction
From Idea to IND & Beyond
SRI Biosciences
Basic
Research
Drug
Discovery
“Institute”
“Biotech Venture”
Drug
Development
Services
“CRO”
© 2016 SRI International
25
SRI Biosciences Capabilities
Wide range of experience
Basic Research
Biomarkers& Diagnostics
CRO Services
Proteomics
Systems Biology
Drug Repurposing
Drug Discovery
NCE & NBE Therapeutics
HCS & HTS
Preclinical Development
PharmaceuticalSciences
PK/DM & Predictive ADMET
Medicinal Chemistry DrugDelivery & Formulations
Small Molecules
Safety Toxicology
Novel Peptides ClinicalChemistry
Bioimaging
Polyclonal Antibodies
CMC & QA/QC
Pharmacology
Vaccines
GLP & GMP
Radiolabeling
Project Management
Clinical & Regulatory
26
© 2016 SRI International
Integrated Pharmaceutical Discovery & Development
Provides seamless transition from idea through the IND
and into the clinic
SRI Capabilities
© 2016 SRI International
Biosimilar Capabilities
Genome Biology 2004,
http://genomebiology.com/2004/6/1/R2
Volume 6, Issue 1, Article R2
Romero et al. R2.9
H. sapiens Pathway: oxidative ethanol degradation I
comment
alcohol dehydrogenase 2: ADH1B
aldehyde dehydrogenase 2
acetaldehyde
NAD
NADH
acetate
NAD
NADH
ATP
coenzyme A
acetyl coenzyme-A synthetase: ACAS2
6.2.1.13
phosphate
reviews
ADP
acetyl-CoA
Locations of Mapped Genes:
reports
• BioInformatics/
Computational
Biology
1.1.1.ethanol
deposited research
Superclasses: Pathways
Created by: wagg on 16-Sep-2003
Comment:
This ethanol degradation pathway begins with conversion of ethanol to acetaldehyde by cytosolic alcohol
dehydrogenase. The resulting acetaldehyde passes into the mitochondrial compartment where it is converted to
acetate (by mitochondrial aldehyde dehydrogenase). Should acetate be activated to acetyl-CoA within the liver, it
would not be oxidized by the Krebs cycle because of the prevailing high ratio of NADH + H / NAD+ within the
liver mitochondrial matrix. Consequently, acetate leaves the mitochondrial compartment and the hepatocyte to be
metabolised by extra-hepatic tissues [ Salway ] . Extrahepatic tissues take up acetate where it is converted to
acetyl-CoA [ Yamashita01 ] .
References
interactions
Oxidative and nonoxidative pathways have been demonstrated in a range of tissues including gastric, pancreatic,
hepatic and lung. Inhibition of oxidative ethanol degradation pathways raises both hepatic and pancreatic FAEE
levels demonstrating that oxidative and nonoxidative pathways are alternative metabolically linked pathways.
Pancreatic ethanol metabolism occurs predominantly by the nonoxidative pathway but oxidative routes to
acetaldehyde have also been demonstrated in the pancreas - the cytochrome P450 2E1 & alcohol dehydrogenase
pathways [ Chrostek03 ] .
refereed research
Best03 : Best CA, Laposata M (2003). "Fatty acid ethyl esters: toxic non-oxidative metabolites of ethanol and markers of ethanol
intake." Front Biosci 8;e202-17. PMID: 12456329
Chrostek03 : Chrostek L, Jelski W, Szmitkowski M, Puchalski Z (2003). "Alcohol dehydrogenase (ADH) isoenzymes and
aldehyde dehydrogenase (ALDH) activity in the human pancreas." Dig Dis Sci 48(7);1230-3. PMID: 12870777
Salway : Salway, J.G. "Metabolism at a Glance, Second Edition." p.90.
Yamashita01 : Yamashita H, Kaneyuki T, Tagawa K (2001). "Production of acetate in the liver and its utilization in peripheral
tissues." Biochim Biophys Acta 1532(1-2);79-87. PMID: 11420176
Figure 3 (see legend on next page)
information
• Fermentation
/Production
Technologies
Four distinct human ethanol degradation pathways have been described - three oxidative pathways and one
nonoxidative pathway. All oxidative pathways mediate the oxidation of ethanol to acetaldehye which is then
oxidized to acetate for subsequent extra-hepatic activation to acetyl-CoA [ Yamashita01 ] . Oxidative pathways
are differentiated based on the enzyme/mechanism by which ethanol is oxidized to acetaldehyde. The present
pathway utilizes cytoplasmic alcohol dehydrogenase with the other two oxidative pathways utilizing endoplasmic
reticulum Microsomal Ethanol Oxidizing System (MEOS) and peroxisomal catalase, respectively. MEOS is also
known as Cytochrome P450 2E1. The nonoxidative pathway is less well characterized but produces fatty acid
ethyl esters (FAEEs) as primary end products [ Best03 ] .
Genome Biology 2004, 6: R2
• OMICS
© 2016 SRI International
Drug Discovery
& Development
Capabilities
SRI Drug Development Pipeline – Track
Record of Success
halofantrine
pralatrexate
tirapazamine
TAS-108
SR13668
Oral Vancomycin
Oral DTPA
SR16157
SR16388
SR13654
BH-0492
Early Discovery
SRI Drugs available for licensing
© 2016 SRI International
NDA • NDA • NDA • NDA • NDA • NDA • NDA
bexarotene
IND • IND • IND • IND • IND • IND • IND • IND
vidarabine
Bloomberg Global Innovation Index
© 2016 SRI International
Top Global Trends in BioPharma
•
•
•
•
•
•
•
•
•
Pharmacoeconomics / Outcomes
Personalized Medicine
Prevention
Patient Centric
Access AND Affordability
Generics
Chronic Disease
Digital Pharma
Biosimilars
© 2016 SRI International
Innovation Case Study examples
•
•
•
Oral DTPA (agent to counter radiation exposure)
Innovation of Diagnostics and Medical Devices (FastCell)
Continuous Drug Manufacturing process (SynFini)
© 2016 SRI International
32
Case Study: New Drug Formulation for Radiation
Exposure
Reformulation of Zn-DTPA into an oral
formulation from an IV medication
Zinc diethylenetriaminepentaacetate (Zn-DTPA) has been
the chemical compound commonly used to treat
radionuclide exposure delivered through an IV. Many
attempts to re-formulate Zn-DTPA into an oral medication
has failed. In 2005, SRI took on the project and was able
to successfully develop and manufacture a novel, oral
formulation of Zn-DTPA that has proven efficacy in
animal studies. SRI identified promising enhancers by
using their “IVtoPO Platform Technology” program to
perform high-throughput solubility and intra-intestinal
permeation screening.
© 2016 SRI International
Case Study: FAST cell ™-CTC Technology
Customized Liquid Biopsy
2 x 10 7 cells
scanned in a
minute
FAST CTC
Analysis
HER2 / CEP17
Morphology/
Pathology
Nano-PCR
Peripheral blood from a cancer patient is collected for multiple endpoint analysis
̶ FAST cell ™ locates CTCs, enables precision analysis, pathological review & confirmation of CTCs
–
–
Staining for protein markers, FISH for genomic amplification and translocation
Sequencing, nano-PCR and expression analysis in development
© 2016 SRI International
Proprietary FAST cell ™ Cytometer
Automated Imaging at High Resolution
Scanning laser spot focuses
on top of transparent substrate
FAST – Fiber Array Scanning Technology
Substrate
Motion
Rotating
Mirror
FAST
Light Collector
Fiber Optic Bundle
ADM
Collimating, Bandpass, collection
Filters/Lens
Multiplex biomarker imaging
Photomultiplier
Tubes (PMT )
Laser speed = 10m sec -1 ~ 1 cm 2 sec -1
F-Theta linearity ~ 0.1%
Spot size ~ 8 µ m
Location accuracy = 40 µ m
Scan Width = 76 mm
CTC
• Cytokeratin (Red)+
• DAPI (Blue)+
• CD45 (Green)WBC
• Cytokeratin (Red)• DAPI (Blue)+
• CD45 (Green)+
Continuous Manufacturing in
Pharmaceutical Research
1800s – 1900s
2000s
The Future
Streamlining the small
molecule drug
discovery progress…
…By creating an end to
end automated
chemical synthesis
platform
Synthetic Chemistry – Status Quo
Batch process methodology hasn’t changed in two
centuries
© 2016 SRI International
SynFini - Revolutionizing Drug Design/Manufacturing
•
Potential Economic Impact
−
−
−
−
•
Save $Bs in drug discovery and development
Reduce time from lab to market
Decrease discovery synthesis time ~80%
Decrease transfer to pilot scale time by ~85%
Stage of Project
−
−
Received SBT funding
DARPA Make-It
•
•
•
Four year, multimillion dollar program
Technology and know how proposed by SRI
Next Steps
−
−
Engage one or more strategic partners
Build industry consortium
Revolutionizing drug
manufacturing for increased
efficiency and reduced costs.
Conclusion
•
Thoughts on Future Innovations in BioPharma
−
Personalized Medicine
− Prevention
− Patient Centric
− Access AND Affordability
− Generics
− Chronic Disease
− Digital Pharma
− Biosimilars
Interface of traditional and emerging disciplines
−
•
Pharmacoeconomics / Outcomes
working together on important problems
to change the world… repeatedly
www.sri.com
Ted Ira
Executive Director of Business Development, Global Partnerships
[email protected]
+1 650.208.9316
39